DeCure's autonomous Cancer AI scientist is researching a drug-repurposing hypothesis for anal neoplasm — screening already-approved drugs against its 29-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAnal neoplasm maps to a 29-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for anal neoplasm is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
hydroxyacid oxidase 1 (HAO1) — HAO1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet fmndrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2NZL · 1.35 Å · ligand FLAVIN MONONUCLEOTIDE (FMN). Experimental structure, not a prediction.
What the evidence adds up to
The 1995 Eastern Cooperative Oncology Group trial enrolled 50 eligible patients with T1-4 N0 M0 anal cancer and treated them with 4000 cGy to the pelvis, anus, and perineum plus a 1000-1300 cGy boost, alongside infusions of 5-fluorouracil and mitomycin-C at the start of radiation and a second 5-fluorouracil infusion 28 days later. Biopsy at 6-8 weeks showed a complete response in 34 of 46 evaluable patients, a partial response in 11, and no response in 1. Seven-year survival for the whole group was 58%, and for partial responders it was 53%; freedom from locoregional progression was 80% at 7 years. White patients and those with favourable performance status had significantly better survival. Positive biopsy led to abdominal-perineal resection.
Later reviews confirm that chemoradiation remains the mainstay for early localised disease, with systemic therapy for metastatic disease and salvage surgery reserved for recurrence after chemoradiation. Anal carcinoma accounts for roughly 2% of gastrointestinal malignancies and less than 7% of anorectal cancers, with squamous cell carcinoma the most common type and an annual incidence of about 1 to 2 per 100,000 persons. Risk factors include human papillomavirus infection, HIV, tobacco use, immunosuppression, female sex, and older age. The pathogenesis is linked to HPV-related inflammation leading to dysplasia and progression to cancer, though many molecular and cellular mechanisms remain unexplored.
Anal intraepithelial neoplasia is the recognised premalignant precursor to invasive squamous cell carcinoma, typically asymptomatic and often found incidentally or through screening of high-risk populations. The optimal management of AIN remains controversial because its natural history is unclear; options range from expectant management to topical therapy, photodynamic therapy, ablation, and surgery. There is no significant body of literature supporting screening, monitoring, or treatment of these precursor lesions, particularly in high-risk groups, and the 2023 review notes that evidence for preventing progression to invasive cancer is lacking. A 2024 review of high-grade squamous intraepithelial lesions similarly calls for individualised interventions and effective follow-up but does not report trial data.
The 2007 overview states that understanding of anal cancer pathogenesis shifted from chronic local inflammation to HPV infection, and that in the majority of cases the condition can be cured with chemotherapy and radiotherapy without surgery. However, the 2022 review on inflammation notes that chronic inflammation from infections, autoimmune diseases, and inflammatory diseases of unknown aetiology promotes tumorigenesis, and that further studies are needed to elucidate pathogenesis and develop immunotherapeutic approaches. What is still missing is prospective data on optimal screening and monitoring of precursor lesions, randomised comparisons of topical versus ablative versus surgical management for AIN and HSIL, and validated biomarkers or stratification tools to identify which patients with early disease can avoid salvage surgery or benefit from intensified systemic therapy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cancer · 1995 · 68 citations · open access
Results of combined modality therapy for patients with anal cancer (E7283). An eastern cooperative oncology group study
AbstractBACKGROUND: This prospective study assessed combined modality therapy of patients with International Union Against Cancer classification T1-4 N0 M0 anal cancer. METHODS: Protocol therapy consisted of a dose of 4000 cGy to the pelvis, anus, and perineum, followed by a 1000-1300 cGy boost. Infusions of 5-fluorouracil and mitomycin-C were administered when radiation therapy began. A second infusion of 5-fluorouracil was administered 28 days later. Biopsy was performed 6-8 weeks after completion of treatment. Positive biopsy findings resulted in abdominal-perineal resection. RESULTS: Survival at 7 years for 50 eligible patients was 58%. White patients and those with favorable performance status had significantly better survival. Of the 46 patients evaluable for response, 34 had a complete response, 11 had a partial response, and 1 had no response. Seven-year survival for partial responders was 53%. Freedom from locoregional progression was 80% at 7 years. CONCLUSION: Treatment with a combination of chemotherapy and radiation therapy is effective for patients with anal cancer. The investigation of methods of improving therapy is warranted.
World Journal of Experimental Medicine · 2024 · 16 citations · open access
Anal carcinoma - exploring the epidemiology, risk factors, pathophysiology, diagnosis, and treatment
AbstractAnal carcinoma is a relatively rare tumor that accounts for approximately 2% of gastrointestinal malignancies and less than 7% of anorectal cancers. Most anal tumors originate between the anorectal junction and the anal verge. Risk factors for the disease include human papillomavirus infection, human immunodeficiency virus, tobacco use, immunosuppression, female sex, and older age. The pathogenesis of anal carcinoma is believed to be linked to human papillomavirus-related inflammation, leading to dysplasia and progression to cancer. Squamous cell carcinoma is the most common type of anal tumor, with an annual incidence of approximately 1 to 2 per 100000 persons. Treatment regarding anal cancer has emerged over time. However, chemoradiation therapy remains the mainstay approach for early localized disease. Patients with metastatic disease are treated with systemic therapy, and salvage surgery is reserved for disease recurrence following chemoradiation. This article aims to provide background information on the epidemiology, risk factors, pathology, diagnosis, and current trends in the management of anal cancer. Future directions are briefly discussed.
AbstractThe aim of this article was to present a summary of the current resources available in the literature regarding the role of inflammation in anal cancer development. Anal cancer is relatively uncommon, accounting for about 2.7% of all reported gastrointestinal cancers in the United States. However, the importance of understanding the pathogenesis and risk factors for anal cancer has been recognized over the last several decades due to a noticed increase in incidence worldwide. Infections, autoimmune diseases, and inflammatory diseases of unknown etiology cause chronic inflammation that promotes tumorigenesis. The association between chronic inflammation and cancer development is widely accepted. It is based on different pathophysiological mechanisms that lead to cellular transformation and changes in immunological response, allowing tumor cells to avoid apoptosis and immune surveillance. However, there are still many molecular and cellular mechanisms that remain largely unexplored. Further studies on this topic could be of tremendous significance in elucidating anal cancer pathogenesis and developing immunotherapeutic approaches for its treatment.
Clinics in Colon and Rectal Surgery · 2018 · 1 citations · open access
Anal Intraepithelial Neoplasia and Squamous Cell Cancer of the Anus
AbstractAnal intraepithelial neoplasia (AIN) is the premalignant condition of the anal squamous tissue. It is associated with the human papilloma virus and is considered the transition prior to the invasive anal squamous cell carcinoma. It is typically asymptomatic and can be either an incidental finding after anorectal surgery or identified when high-risk patient populations are screened. Once AIN is diagnosed, the optimal management remains controversial, partly because the natural history of the disease is unclear. Surgical management of the disease has essentially been replaced by more conservative treatment options and can range from expectant management to topical therapy to photodynamic therapy. The aim of this article is to review the varied treatment options and to briefly review prevention strategies.
AbstractThis chapter gives an overview of the aetiology, presentation, and classification of anal squamous carcinoma (SCC) and the other less common anal tumors. The treatment of anal SCC has changed dramatically during the last ten years and the rationale for these changes is discussed. The identification of anal pre-cancerous lesions and strategies for their management are described.
Journal of Surgical Oncology · 2023 · 0 citations · open access
Current monitoring and treatment for anal intraepithelial neoplasms
AbstractAnal intraepithelial neoplasms (AIN) are precursors to anal cancer. To date, there is not a significant body of literature to support screening, monitoring, and treatment of these precursor lesions, particularly in high risk populations. This review will detail the current monitoring and indications for treatment of such lesions, with the goal of preventing progression to invasive cancer.
DOAJ (DOAJ: Directory of Open Access Journals) · 2024 · 0 citations
Research status of treatment modalities for anal high-grade squamous intraepithelial lesion
Abstract［Abstract］ Anal high-grade squamous intraepithelial lesion (HSIL), encompassing grades 2 and 3 of anal intraepithelial neoplasia, represents a precancerous condition for anal squamous cell carcinoma. Actively pursuing individualized interventions and effective follow-up management for these patients is significant. Based on relevant literature, this article reviews the current research status of topical medications, ablation, and surgical treatment for anal HSIL, aiming to provide insights for optimizing the treatment of this disease in the future.
Squamous cell carcinoma of the anus: diagnosis and treatment
AbstractThis paper presents an overview of squamous cell carcinoma (SCC) of the anus (anal cancer), a rare cancer accounting for less than 2% of all lower gastrointestinal malignancies. Our understanding of the pathogenesis and management of this cancer has dramatically changed over the past 35 years, with studies showing that the development of anal cancer is associated with infection by human papillomavirus, as opposed to previous beliefs that it developed from chronic local inflammation of the perianal area. These findings have impacted on treatment modalities so that in the majority of cases the condition can be cured with a combination of chemotherapy and radiotherapy, without the need for surgery.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, resolved on OpenAlex.
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